Herpes B virus (BV) is a pathogen of macaques that is endemic in most macaque colonies. In macaques, BV infection is typically self-limiting. In contrast, BV can zoonotically infect humans and has a fatality rate of approximately 80%. Due to the severity of BV infections, the virus is classified by the CDC as a Risk Group 4 agent and may only be propagated in Biosafety Level 4 containment. Macaque monkeys are the most commonly used non-human primate in biomedical research. Their use is affected by the potential for BV infection to animal care staff and those handling macaque cells and tissues. The NIH funds several programs to generate macaque colonies free of BV. Unfortunately, the demand for BV-free animals far outstrips supply. BV-free animals are also expensive. The long-term goal of this project is to develop a BV vaccine that will protect macaque monkeys from BV infection. This will greatly improve the safety for animal care staff, increase the supply of SPF monkeys and decrease their cost. Toward this goal, we have generated a recombinant simian foamy virus (SFV) that expresses the immunogenic glycoprotein D (gD) from BV (BV gD/SFV). The objective of this application is to determine the ability of BV gD/SFV to induce a protective immune response in a model animal. To accomplish this objective, we will carry out the following two specific aims: 1) to determine the potency of BV gD/SFV vaccine in rabbits;2) to determine the efficacy of the vaccine to protect rabbits from a lethal challenge of BV. The proposed project is significant because protecting monkeys from becoming infected with BV will greatly improve the ability to develop and maintain BV-free macaque colonies. The proposed study is innovative because of the focus on the development a vaccine that will protect monkeys from BV infection but not affect their use in future experimental protocols. Moreover, SFV-based vectors have been evaluated for use as gene therapy vectors but not as vaccine vectors. The successful completion of this project will provide data to support further studies to test the efficacy of the SFV- based vaccine in macaque monkeys. PUBLIC HEALTH RELEVANCE: Macaque monkeys are the most commonly used non human primate biomedical research. However, they are endemically infected with herpes B virus that causes a deadly infection in humans. A vaccine that protects monkeys from herpes B virus infection will greatly improve the safety of those working with these monkeys and their tissues, and thus improve the utility of these animals.